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ROR1 sustains RTK-mediated survival signaling in lung adenocarcinoma

Research Project

Project/Area Number 25461187
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNagoya University

Principal Investigator

YAMAGUCHI TOMOYA  名古屋大学, 医学(系)研究科(研究院), 特任助教 (70452191)

Co-Investigator(Renkei-kenkyūsha) YANAGISAWA Kiyoshi  名古屋大学, 大学院医学系研究科, 講師 (20372112)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肺腺がん / ROR1 / カベオラ / EGFR-TKI / 薬剤耐性 / 肺腺癌 / TTF-1 / 受容体型チロシンキナーゼ / EGFR / RTKの活性化 / RTKのクロストーク
Outline of Final Research Achievements

The receptor tyrosine kinase-like orphan receptor 1 (ROR1) sustains prosurvival signaling directly downstream of the lineage-survival oncogene NKX2-1/TTF-1 in lung adenocarcinoma. We analyzed the effects of siROR1 treatment on the phosphorylation state using a human phospho-RTK array, which revealed a significant decrease in the phosphorylation of multiple RTKs in both NCI-H1975 and PC-9 lung adenocarcinoma cells. We found that ROR1 knockdown effectively overcame ligand-mediated EGFR-TKI resistance in PC-9 or NCI-H1975 cell. These results suggest that ROR1 repression inhibits lung adenocarcinoma cells with acquired EGFR-TKI resistance through bypass pathways. Finally, we also found that ROR1 knockdown significantly decreased the protein expression of CAV1, the essential structural component of caveolae, in lung adenocarcinoma cells.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (9 results)

All 2016 2015 2014 2013

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] ROR1 sustains caveolae and survival signaling as a scaffold of cavin-1 and caveolin-12016

    • Author(s)
      Yamaguchi T, Lu C, Yanagisawa K, Can Lu, Usukura J, Cheng J, Hotta N, Shimada Y, Ida R, Isomura H, Suzuki M, Fujimoto T, Takahashi T
    • Journal Title

      Nat Commun

      Volume: 7 Issue: 1 Pages: 10060-10060

    • DOI

      10.1038/ncomms10060

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] NKX2-1/TTF-1: an enigmatic oncogene that functions as a double-edged sword for cancer cell survival and progression2013

    • Author(s)
      Yamaguchi T, Hosono Y, Yanagisawa K, Takahashi T
    • Journal Title

      Cancer Cell

      Volume: 23 Issue: 6 Pages: 718-723

    • DOI

      10.1016/j.ccr.2013.04.002

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] ROR1 functions as a scaffold of cavin-1 and CAV1, sustaining caveolae and RTK-mediated survival signaling in lung cancer2016

    • Author(s)
      Yamaguchi T, Lu C, Ida L, Yanagisawa K, Usukura J, Cheng J, Hotta N, Shimada Y, Isomura H, Suzuki M, Fujimoto T and Takahashi T
    • Organizer
      AACR-IASLC Joint Lung Cancer Conference
    • Place of Presentation
      San Diego, CA, アメリカ
    • Year and Date
      2016-01-04
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ROR1によるカベオラ形成を通じたRTK活性化維持を標的としたEGFR-TKI耐性の克服2015

    • Author(s)
      山口知也、柳澤聖、Can Lu、井田梨沙、磯村久徳、鈴木元、藤本豊士、高橋隆
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] TTF-1/NKX2-1-induced ROR1 is required to sustain EGFR survival signaling in lung adenocarcinoma2013

    • Author(s)
      Tomoya Yamaguchi, and Takashi Takahashi
    • Organizer
      International Scientific Coordination Network (ISCN) 3rd GDRI French Japanese Cancer Meeting
    • Place of Presentation
      Toulouse, France
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] -肺がんの個別化医療-肺腺がんにおけるTTF-1/NKX2-1の相反する2つの機能2015

    • Author(s)
      山口知也、高橋隆
    • Total Pages
      150
    • Publisher
      最新医学社
    • Related Report
      2015 Annual Research Report
  • [Book] 最新肺癌学 -基礎と臨床の最新研究動向- 肺腺癌の分子病態におけるTTF-1の二面性2013

    • Author(s)
      山口知也、高橋隆
    • Total Pages
      759
    • Publisher
      日本臨牀
    • Related Report
      2013 Research-status Report
  • [Book] 分子呼吸器病 肺腺癌の生存シグナルを支えるROR1キナーゼ2013

    • Author(s)
      山口知也、高橋隆
    • Total Pages
      158
    • Publisher
      先端医学社
    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] 癌細胞のカベオラの形成を特異的に抑制する化合物のスクリーニング方法2014

    • Inventor(s)
      高橋隆、山口知也
    • Industrial Property Rights Holder
      名古屋大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-217313
    • Filing Date
      2014-10-24
    • Related Report
      2014 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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